PB1987: EVALUATION OF THE SECOND GENERATION TYROSINE KINASE INHIBITOR IN IMATINIB-RESISTANT OR -INTOLERANT CHRONIC PHASE, CHRONIC MYELOID LEUKEMIA ADULT PATIENTS
Authors: Soraya Bougherira
Journal: HemaSphere (2023)

Topic: 8. Chronic myeloid leukemia - Clinical Background:BCR-ABL targeted Tyrosine Kinase Inhibitors like Imatinib have changed the landscape of Chronic Myeloid Leukemia (CML) treatment and produced improved rates of long-term response and survival. Results at 8 years of the IRIS study demonstrated the superiority of Imatinib (IM) with a complete cytogenetic response at 76%, overall survival at 85% and progression-free survival at 92%. Despite this progress, 45% of patients ultimately discontinue IM, mostly due to unsatisfactory responses and/or toxicities leading to a therapeutic change. The use of second-generation TKIs as salvage has improved the responses of CML patients treated with TKIs. These agents are suitable major option if resistance or IM intolerance occurs in CML. They are now introduced as first-line therapy in CP-CML, witch is promising for long-term survival. Aims: Evaluate the efficacy and asses safety profile of 2G-TKI in patients with CP-CML following IM failure or intolerance. Methods: This is a prospective cohort study, from 2012 to 2015, monocentric, carried out at the Hematology department of the Annaba University Hospital. All adult patients with chronic CML, resistant and or intolerant to Imatib were included. A card was designed for each patient eligible for the study, describing the diagnostic, therapeutic and progressive characteristics. Patients were classified according to prognostic classifications (Sokal, Hasford, EUTOS, ELTS and Hammersmith Hospital). The therapeutic response was seen according to the 2013 ELN criteria, adapted to our conditions. Results: 53 patients divided between 28 men and 25 women with a sex ratio of 1.2, the median age was 48 years. The translocation (9; 22) (looked for by conventional or molecular cytogenetics, FISH) was positive in 100% of cases with 10% ACA at diagnosis. The BCR-ABL1 transcript was identified in 47 pts with a similar distribution (47 and 41%) of types b3a2 and b2a2 respectively. The Sokal score was low in 21%, intermediate in 36% of pts and high in 40% of cases. TKI2 were prescribed in the 2nd line after failure of IM in 45 pts (85%) or in case of intolerance in 8 patients (15%). The median time from IM to initiation of TKI2 was 49.7 months. Dasatinib treatment concerned 30 patients, Nilotinib was prescribed in 23 patients. We evaluated the Hammersmith score in 33 pts, of which 8 or 24% had a low risk. The therapeutic results of DASA and NILO were similar and resulted in overall RHC, RCyC and RMM in 87%, 80% and 58% of cases, respectively. The time to obtain these responses was more or less short. According to the ELN 2013 criteria, the response was ranked optimal, warning and failure in 64%, 11% and 25%, respectively. The safety profile varies depending on the TKI used, the majority of AEs were graded ½. Hematologic toxicity related to DASA is dominated by thrombocytopenia in 40%, half of which was grade ¾. Non-hematological adverse events mainly represented by pleural effusion and digestive disorders. NILO also caused hematological and extra-hematological toxicities, in particular skin rash, hyper bilirubinemia, hyper glycemia and disturbances in the lipid balance. Progression-free survival, event-free survival and 5-year overall survival were 66.7, 92.2 and 81.39%, respectively. The median survival is not reached. Summary/Conclusion: The introduction of TKIs had an important impact on the prognosis of patients with CML over the last years. We confirm through this single-center study that DASA and NILO are effective therapy in patients with CP-CML, resistant and/ or intolerant to IM. They exhibit a favorable safety profile. These results strongly support the use of these TKI2 as front-line therapy in CP-CML. Keywords: Imatinib resistance, Chronic myeloid leukemia, Nilotinib, Molecular remission